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Using Genetic Variation to Explore the Causal Effect of Maternal Pregnancy Adiposity on Future Offspring Adiposity: A Mendelian Randomisation Study

Author

Listed:
  • Rebecca C Richmond
  • Nicholas J Timpson
  • Janine F Felix
  • Tom Palmer
  • Romy Gaillard
  • George McMahon
  • George Davey Smith
  • Vincent W Jaddoe
  • Debbie A Lawlor

Abstract

Background: It has been suggested that greater maternal adiposity during pregnancy affects lifelong risk of offspring fatness via intrauterine mechanisms. Our aim was to use Mendelian randomisation (MR) to investigate the causal effect of intrauterine exposure to greater maternal body mass index (BMI) on offspring BMI and fat mass from childhood to early adulthood. Methods and Findings: We used maternal genetic variants as instrumental variables (IVs) to test the causal effect of maternal BMI in pregnancy on offspring fatness (BMI and dual-energy X-ray absorptiometry [DXA] determined fat mass index [FMI]) in a MR approach. This was investigated, with repeat measurements, from ages 7 to 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 2,521 to 3,720 for different ages). We then sought to replicate findings with results for BMI at age 6 in Generation R (n = 2,337 for replication sample; n = 6,057 for total pooled sample). Conclusions: Our findings provide little evidence to support a strong causal intrauterine effect of incrementally greater maternal BMI resulting in greater offspring adiposity. Using a Mendelian randomization approach, Rebecca Richmond and colleagues find limited evidence for a causal effect of maternal pregnancy adiposity on future offspring adiposity during childhood and adolescence.Why Was This Study Done?: What Did the Researchers Do and Find?: What Do These Findings Mean?:

Suggested Citation

  • Rebecca C Richmond & Nicholas J Timpson & Janine F Felix & Tom Palmer & Romy Gaillard & George McMahon & George Davey Smith & Vincent W Jaddoe & Debbie A Lawlor, 2017. "Using Genetic Variation to Explore the Causal Effect of Maternal Pregnancy Adiposity on Future Offspring Adiposity: A Mendelian Randomisation Study," PLOS Medicine, Public Library of Science, vol. 14(1), pages 1-24, January.
    • Handle: RePEc:plo:pmed00:1002221
    DOI: 10.1371/journal.pmed.1002221
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    1. David M Evans & Marie Jo A Brion & Lavinia Paternoster & John P Kemp & George McMahon & Marcus Munafò & John B Whitfield & Sarah E Medland & Grant W Montgomery & The GIANT consortium & The CRP consort, 2013. "Mining the Human Phenome Using Allelic Scores That Index Biological Intermediates," PLOS Genetics, Public Library of Science, vol. 9(10), pages 1-15, October.
    2. Debbie A Lawlor & Nicholas J Timpson & Roger M Harbord & Sam Leary & Andy Ness & Mark I McCarthy & Timothy M Frayling & Andrew T Hattersley & George Davey Smith, 2008. "Exploring the Developmental Overnutrition Hypothesis Using Parental–Offspring Associations and FTO as an Instrumental Variable," PLOS Medicine, Public Library of Science, vol. 5(3), pages 1-10, March.
    3. Douglas Staiger & James H. Stock, 1997. "Instrumental Variables Regression with Weak Instruments," Econometrica, Econometric Society, vol. 65(3), pages 557-586, May.
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